Antimicrobial peptides (AMPs) are oligopeptides with a varying number of amino acids (from five to over a hundred). AMPs have a broad spectrum of targeted organisms ranging from viruses to parasites.
The discovery of AMPs dates back to 1939 when Dubos extracted an antimicrobial agent from a soil Bacillus strain. This extract was demonstrated to protect mice from pneumococci infection. In the following year, Hotchkiss and Dubos fractionated this extract and identified an AMP which was named gramicidin. Despite some reported toxicity associated with intraperitoneal application, gramicidin was found to be beneficial for topical treatment of wounds and ulcers. In 1941, another AMP, tyrocidine, was discovered and found to be effective against both gram-negative and gram-positive bacteria. However, tyrocidine was toxic to human blood cells. In the same year, another AMP was isolated from a plant Triticum aestivum, which was later named purothionin and found to be beneficial against fungi and some pathogenic bacteria.
The first reported animal-originated AMP is defensin, which was isolated from rabbit leukocytes in 1956. In the following years, bombinin from epithelia and lactoferrin from cow milk were both described. During the same time, it was also proven that human leukocytes contain AMPs in their lysosomes.
Most AMPs are produced by specific cells while the production of some AMPs is inducible. Several types of eukaryotic cells are involved in AMP production such as lymph, epithelial cells in gastrointestinal and genitourinary systems, phagocytes, and lymphocytes of the immune system. In addition to direct involvement in innate immunity, AMPs have also been found to influence the host's inflammatory responses during an infection. It is known that lipopolysaccharide (LPS) molecules released from bacteria as a result of antibiotic treatment or host immunity, can induce AMP production in mammals.
Most AMPs are characterized as one of the following four types based on their secondary structures: β-sheet, α-helix, extended, and loop. Among these structural groups, α-helix and β-sheet structures are more common. β-sheet peptides are composed of at least two β-strands with disulfide bonds between these strands.
The best-known examples of such AMPs are protegrin, magainin, cyclic indolicin, and coiled indolicin. Some AMPs contain two different structural components. In addition, many peptides form their active structure only when they interact with the membranes of target cells. For example, indolicin shows globular and amphipathic conformation in aqueous solutions while it is wedge-shaped in lipid bilayer mimicking environments. This AMP also changes its conformation during interaction with DNA.
Understanding the impact of the molecular level of AMPs on their mechanism(s) of action is needed in order to develop a new class of antibiotics. Recently, a correlation between antimicrobial activity and amyloid formation was described.
Fibrils and oligomers amyloids are involved in more than 20 fatal diseases and astonishingly, also in controlled cellular processes in all kingdoms of life. Interestingly, peptides of several well-known human host defense form amyloid-like fibrils, and several well-known human disease-related amyloids, including AP involved in Alzheimer's, display antimicrobial action.